Life Sciences Insight

Seagen joins SpringWorks’ long list of BCMA combo partners

Seagen has teamed up with SpringWorks Therapeutics to test its anti-BCMA antibody in combination with a gamma secretase inhibitor. The planned phase 1 builds on evidence that inhibiting gamma secretase prevents the cleavage and shedding of BCMA from the surface of myeloma cells.

Pfizer spinout SpringWorks has taken its gamma secretase inhibitor nirogacestat as far as an ongoing phase 3 clinical trial in patients with desmoid tumors as a single agent, but the drug is now perhaps better known for its potential role as an enhancer of BCMA therapies. GlaxoSmithKline, Johnson & Johnson, Pfizer, Allogene Therapeutics and Precision Biosciences have accessed the asset.

Those alliances are testing nirogacestat in combination with anti-BCMA antibody-drug conjugates, bispecific antibodies and CAR-T therapies. The Seagen collaboration adds a new modality to SpringWorks’ roster of BCMA combination trials.

“Our goal is to meaningfully improve clinical outcomes for patients with multiple myeloma and we look forward to generating clinical data using nirogacestat in combination with BCMA-directed therapies across modalities,” SpringWorks CEO Saqib Islam said in a statement.

Seagen will test nirogacestat in combination with its BCMA antibody SEA-BCMA. The drug is designed to enhance antibody-dependent cellular cytotoxicity. In describing the ongoing phase 1 clinical trial of the candidate, researchers said frail multiple myeloma patients “face a particularly high unmet need, given the toxicity profiles of many agents.”  

In theory, adding nirogacestat to SEA-BCMA could boost the efficacy of the Seagen drug without making the toxicity profile intolerable. Seagen will start testing that idea later this year when it sponsors a phase 1 trial to assess the safety, tolerability and preliminary efficacy of the combination. Seagen will foot the costs of the trial, except expenses related to the manufacturing of nirogacestat and certain outlays linked to intellectual property rights.

SEA-BCMA was previously tested in combination with Unum Therapeutics’ autologous T-cell product ACTR087. However, ACTR087 ran into safety problems in other trials and was deprioritized by Unum. The SEA-BCMA combination trial was later terminated for “business reasons.”